Foods
·
2023
·Vol. 12
·期 13
·2521
·
IF 5.2
Xiaobo Li,Miao Zhang,Haizhen Mo,Hongbo Li,Dan Xu,Liangbin Hu
The increasing incidence of diseases caused by highly carcinogenic aflatoxin M1(AFM1) in food demands a simple, fast, and cost-effective detection technique capable of sensitively monitoring AFM1. Recent works predominantly focus on the electrochemical aptamer-based biosensor, which still faces challenges and high costs in experimentally identifying an efficient candidate aptamer. However, the direct electrochemical detection of AFM1has been scarcely reported thus far. In this study, we observed a significant influence on the electrochemical signals of ferric ions at a gold nanoparticle-modified glassy carbon electrode (AuNPs/GCE) by adding varying amounts of AFM1. Utilizing ferricyanide as a sensitive indicator of AFM1, we have introduced a novel approach for detecting AFM1, achieving an unprecedentedly low detection limit of 1.6 × 10−21g/L. Through monitoring the fluorescence quenching of AFM1with Fe3+addition, the interaction between them has been identified at a ratio of 1:936. Transient fluorescence analysis reveals that the fluorescence quenching process is predominantly static. It is interesting that the application of iron chelator diethylenetriaminepentaacetic acid (DTPA) cannot prevent the interaction between AFM1and Fe3+. With a particle size distribution analysis, it is suggested that a combination of AFM1and Fe3+occurs and forms a polymer-like aggregate. Nonetheless, the mutual reaction mechanism between AFM1and Fe3+remains unexplained and urgently necessitates unveiling. Finally, the developed sensor is successfully applied for the AFM1test in real samples, fully meeting the detection requirements for milk.Keywords:aflatoxin M1;electrochemical detection;gold nanoparticles;Fe3+
研究领域:
食品安全
·
分析化学
·
电化学
·
纳米技术
·
毒理学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Lei Zhou,Leyuan Huang,Guanfeng He,Haixin Li,Manchun Liu,Jingwen Xu
Background Allergic rhinitis (AR) is a common IgE-mediated inflammatory disease of the nasal mucosa, involving immune–neural interactions such as mast cell activation, cytokine release, and transient receptor potential vanilloid 1 (TRPV1)-mediated neuronal sensitization. Xiao-Qing-Long-Tang (XQLT) is a classical traditional Chinese medicine used clinically for AR. However, its mechanisms, particularly in macrophage regulation and TRPV1 activity, remain not fully understood. Objective This study aimed to evaluate the therapeutic effects of XQLT in an ovalbumin (OVA)-induced AR mouse model and to investigate its molecular mechanisms focusing on immune regulation, macrophage-mediated inflammation, and TRPV1 channel activity. Methods The chemical composition of XQLT was analyzed by UPLC-Q Exactive Orbitrap-HRMS system. The therapeutic effectiveness of XQLT was assessed in an OVA-induced AR mouse model. Clinical symptoms, serum biomarkers (OVA-sIgE, interleukin-4 (IL-4), histamine), and histopathological changes were assessed. Transcriptomic analysis of nasal mucosa was performed to explore molecular pathways. The anti-inflammatory effects of XQLT were evaluated in LPS-stimulated RAW264.7 and bone marrow–derived macrophages by measuring NO, cytokine expression, and NF- κ B activation. TRPV1 involvement was examined using immunohistochemistry in AR mice model, calcium imaging in HEK293 cells overexpressing TRPV1, as well as molecular docking. Results XQLT treatment significantly reduced nasal rubbing and sneezing frequencies in AR mice, decreased serum OVA-sIgE, IL-4, and histamine levels, and ameliorated nasal and lung histopathological remodeling without observable toxicity. Transcriptomic profiling revealed that XQLT modulated DEGs associated with immune response, inflammatory signaling, olfactory transduction, and sensory perception of pain. In macrophages, XQLT suppressed LPS-induced NO production, downregulated IL-6, IL-1 β , CCL2, iNOS, and COX-2 expression, and inhibited NF- κ B nuclear translocation. Importantly, XQLT reduced TRPV1 expression in AR nasal mucosa and inhibited TRPV1-mediated calcium influx in HEK293 TRPV1-overexpressing cells. Zingiberis Rhizoma (Ganjiang) was identified as a key herb contributing to TRPV1 inhibition in XQLT, supported by molecular docking analysis. Conclusion XQLT alleviates AR symptoms and tissue remodeling through coordinated suppression of macrophage-mediated inflammation and TRPV1-dependent neurogenic pathways. These findings provide novel mechanistic insights into XQLT as a safe and promising multi-target therapy for AR.
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Lei Wang,Jinchun Wang,Lei Han,Tong Chen
The present work was conducted to research the potential mechanism of palmatine (PAL) on lipopolysaccharide (LPS)-caused acute lung injury (ALI). Network pharmacology and bioinformatic analyses were carried out. Mice were intragastrically treated with PAL and intratracheally stimulated with LPS. LPS-induced RAW264.7 cells were employed for the in vitro model. The MPO activity, W/D ratio, neutrophils, total cell number in BALF, and histopathological alteration were examined. The levels of TNF-α, IL-1β, IL-6, IL-18, IL-4, and IL-10 in serum, BALF, and supernatant were examined by ELISA. The mRNA expressions of iNOS, CD68, Arg1, Ym1, and CD206 and protein expressions of NAMPT, TLR2, CCR1, and NLRP3 inflammasome were detected by PCR, WB, and immunofluorescence. The NAMPT inhibitor FK866, TLR2 inhibitor C29, CCR1 inhibitor BX471, NAMPT-overexpression (OE) plasmid, and TLR2-OE plasmid were used for mechanism research. As a result, PAL relieved the symptoms of ALI. PAL inhibited M1 phenotype indices and promoted M2 phenotype indices in both LPS-induced mice and RAW264.7 cells. PAL also inhibited the expressions of NAMPT, TLR2, CCR1, and NLRP3 inflammasome. The treatments with FK866, NAMPT-OE plasmid, C29, TLR2-OE plasmid, and BX471 proved that PAL exerted its effect via NAMPT/TLR2/CCR1. Molecular docking suggested that PAL might combine with NAMPT. In conclusion, PAL ameliorated LPS-induced ALI by inhibiting M1 phenotype macrophage polarization via NAMPT/TLR2/CCR1 signaling.
研究领域:
药理学
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免疫学
·
呼吸病学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Jia-Nan Song,Kun Liu,Jie Mei,Luozixian Wang,Jiao Lin,Ping Du,Yung-Chiang Liu,Yafan Wan,Raymond C. B. Wong,Ji-Ye Yin,Peng-Yuan Wang
Biophysical and biochemical cues modulate mammalian cell behavior and phenotype simultaneously. Macrophages, indispensable cells in the innate immune system, respond to external threats such as bacterial infections and implanted devices, undergoing the classical M1 polarization to become a pro-inflammatory phenotype. In the study, lipopolysaccharide (LPS)-induced M1 polarization was examined using RAW264.7, THP-1, and primary human PBMCs on a family of artificial extracellular matrix (ECM), named colloidal self-assembled patterns (cSAPs). The results showed that cSAPs were biocompatible, which cannot induce M1 or M2 polarization. Interestingly, specific cSAPs (e.g., cSAP3) suppress the level of M1 polarization (i.e., reduced nitric oxide production, down-regulated gene expression of iNOS, IL-6, TNF-α, IL-1β, and TLR4, and reduced proportion of CD11b+CD86+ cells). Transcriptome analysis showed that cell adhesion and cell-ECM interaction participated in the M1 polarization, and the mechano-sensitive genes such as PIEZO1 were down-regulated on the cSAP3. More interestingly, these genes were also down-regulated under LPS stimulation, indicating that cells became insensitive to the LPS. The abovementioned results indicate that the defined physicochemical cues can govern macrophage polarization. This study illustrates a potential surface design at biointerface, which is critical in tissue engineering and materiobiology. The outcome is also inspiring in ECM-mediated immune responses.
研究领域:
免疫学
·
组织工程
·
生物材料
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 10
·4018
·
IF 4.6
Lingna Xie,Guangrong Liu,Zebin Huang,Zhenyuan Zhu,Kaiye Yang,Yiheng Liang,Yani Xu,Lanyue Zhang,Zhiyun Du
Anti-tumor activity ofTremella fuciformispolysaccharides (TFPS) has been widely reported, but its mechanism remains poorly understood. In this study, we established an in vitro co-culture system (B16 melanoma cells and RAW 264.7 macrophage-like cells) to explore the potential anti-tumor mechanism of TFPS. Based on our results, TFPS exhibited no inhibition on the cell viability of B16 cells. However, significant apoptosis was observed when B16 cells were co-cultured with TFPS-treated RAW 264.7 cells. We further found that mRNA levels of M1 macrophage markers including iNOS and CD80 were significantly upregulated in TFPS-treated RAW 264.7 cells, while M2 macrophage markers such as Arg-1 and CD 206 remained unchanged. Besides, the migration, phagocytosis, production of inflammatory mediators (NO, IL-6 and TNF-α), and protein expression of iNOS and COX-2 were markedly enhanced in TFPS-treated RAW 264.7 cells. Network pharmacology analysis indicated that MAPK and NF-κB signaling pathways may be involved in M1 polarization of macrophages, and this hypothesis was verified by Western blot. In conclusion, our research demonstrated that TFPS induced apoptosis of melanoma cells by promoting M1 polarization of macrophages, and suggested TFPS may be applied as an immunomodulatory for cancer therapy.Keywords:Tremella fuciformispolysaccharide;immunoregulation;co-culture;macrophages;B16
研究领域:
免疫学
·
肿瘤学
·
药理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Jiabao Dong,Xupeng Chai,Yucheng Xue,Shiyun Shen,Zhuo Chen,Zetao Wang,Eloy Yinwang,Shengdong Wang,Liang Chen,Fengfeng Wu,Hengyuan Li,Zehao Chen,Jianbin Xu,Zhaoming Ye,Xiongfeng Li,Qian Lu
Adoptive cellular therapy is a promising strategy for cancer treatment. However, the effectiveness of this therapy is limited by its intricate and immunosuppressive tumor microenvironment. In this study, a targeted therapeutic strategy for macrophage loading of drugs is presented to enhance anti-tumor efficacy of macrophages. K7M2-target peptide (KTP) is used to modify macrophages to enhance their affinity for tumors. Pexidartinib-loaded ZIF-8 nanoparticles (P@ZIF-8) are loaded into macrophages to synergistically alleviate the immunosuppressive tumor microenvironment synergistically. Thus, the M1 macrophages decorated with KTP carried P@ZIF-8 and are named P@ZIF/M1-KTP. The tumor volumes in the P@ZIF/M1-KTP group are significantly smaller than those in the other groups, indicating that P@ZIF/M1-KTP exhibited enhanced anti-tumor efficacy. Mechanistically, an increased ratio of CD4+ T cells and a decreased ratio of MDSCs in the tumor tissues after treatment with P@ZIF/M1-KTP indicated that it can alleviate the immunosuppressive tumor microenvironment. RNA-seq further confirms the enhanced immune cell function. Consequently, P@ZIF/M1-KTP has great potential as a novel adoptive cellular therapeutic strategy for tumors.
研究领域:
癌症生物学
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药学
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免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CANCER IMMUNOLOGY IMMUNOTHERAPY
·
2024
·Vol. 73
·期 7
·1-24
·
IF 4.6
Liu Hongxu,Yao Maojin,Ren Jiaoyan
The majority of the immune cell population in the tumor microenvironment (TME) consists of tumor-associated macrophages (TAM), which are the main players in coordinating tumor-associated inflammation. TAM has a high plasticity and is divided into two main phenotypes, pro-inflammatory M1 type and anti-inflammatory M2 type, with tumor-suppressive and tumor-promoting functions, respectively. Considering the beneficial effects of M1 macrophages for anti-tumor and the high plasticity of macrophages, the conversion of M2 TAM to M1 TAM is feasible and positive for tumor treatment. This study sought to evaluate whether the glycopeptide derived from simulated digested Codonopsis pilosula extracts could regulate the polarization of M2-like TAM toward the M1 phenotype and the potential regulatory mechanisms. The results showed that after glycopeptide dCP1 treatment, the mRNA relative expression levels of some M2 phenotype marker genes in M2-like TAM in simulated TME were reduced, and the relative expression levels of M1 phenotype marker genes and inflammatory factor genes were increased. Analysis of RNA-Seq of M2-like TAM after glycopeptide dCP1 intervention showed that the gene sets such as glycolysis, which is associated with macrophage polarization in the M1 phenotype, were significantly up-regulated, whereas those of gene sets such as IL-6-JAK-STAT3 pathway, which is associated with polarization in the M2 phenotype, were significantly down-regulated. Moreover, PCA analysis and Pearson's correlation also indicated that M2-like TAM polarized toward the M1 phenotype at the transcriptional level after treatment with the glycopeptide dCP1. Lipid metabolomics was used to further explore the efficacy of the glycopeptide dCP1 in regulating the polarization of M2-like TAM to the M1 phenotype. It was found that the lipid metabolite profiles in dCP1-treated M2-like TAM showed M1 phenotype macrophage lipid metabolism profiles compared with blank M2-like TAM. Analysis of the key differential lipid metabolites revealed that the interconversion between phosphatidylcholine (PC) and diacylglycerol (DG) metabolites may be the central reaction of the glycopeptide dCP1 in regulating the conversion of M2-like TAM to the M1 phenotype. The above results suggest that the glycopeptide dCP1 has the efficacy to regulate the polarization of M2-like TAM to M1 phenotype in simulated TME.
研究领域:
免疫学
·
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biochemistry and Biophysics Reports
·
2023
·
IF 2.7
Ke Zhang,Youyang Liu,Yunlu Zhao,Qi Guo,Shengjun An,Shuhui Wu
Many chronic inflammatory diseases, such as autoimmune inflammation, are associated with M1 macrophages, and the key to their treatment is blocking inflammation. Oxymatrine (OMT), a traditional Chinese medicine, has a marked anti-inflammatory effect. However, its anti-inflammatory target and mechanism in M1 cells remain unclear, which limits its clinical application. In this study, we investigated the anti-inflammatory effects of oxymatrine (OMT) on the M1 inflammatory response. We also determined the relationship between OMT treatment and the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) pathway with OMT treatment. To this end, we induced the differentiation of human peripheral blood monocytes (THP-1) into M1 cells. THP-1 cells were induced with a phorbol ester (phorbol-12-myristate-13-acetate (PMA)) and differentiated into naïve M0 macrophages. M0 cells were induced into M1 cells using lipopolysaccharide (LPS). The experimental groups were divided into the M0 macrophage group (NC), M1 inflammatory response group (LPS group), and M1 group treated with different concentrations of OMT (LPS + OMT-L, LPS + OMT-M, LPS + OMT-H). The cells in the OMT-treated groups were treated with OMT for 6 h, followed by LPS for 24 h, and the LPS group was treated with LPS only. The resulting supernatants and cells were collected. The secretion levels of NO were detected by the Griess method and the secretion levels of TNF-α and IL-1β in the supernatants were detected by the ELISA method. The secretion levels of these inflammatory factors were reduced in every OMT-treated group compared to the LPS group (P < 0.01), and the most significant reductions were found in the OMT-H group (P < 0.0001). By western blotting, the protein expression levels of TLR4, NF-κB, NLRP3, and Caspase-1 were all found to be downregulated in the cells of OMT-treated groups compared to the LPS group (P < 0.0001). In situ changes in NLRP3 expression were observed using immunofluorescence. The fluorescence intensity of NLRP3 in M1 cells was weaker in all OMT intervention groups than in the LPS group (P < 0.001). In conclusion, OMT has significant anti-inflammatory effects on the M1 inflammatory responses, and the TLR4/NF-κB/NLRP3 pathway was blocked proportional to the concentration of OMT.
研究领域:
免疫学
·
药理学
·
细胞生物学
·
炎症性疾病
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产品关联
DOI
PubMed
高影响因子
Journal of Integrative Neuroscience
·
2024
·Vol. 23
·期 10
·185
·
IF 2.5
Yangzhi Xie,Hao Zhang,Jiacheng Chen,Sicong Xu,Yan Luo
Background: Luteolin is a natural flavonoid and its neuroprotective and anti-inflammatory effects have been confirmed to mitigate neurodegeneration. Despite these findings, the underlying mechanisms responsible for these effects remain unclear. Toll-like receptor 4 (TLR4) is widely distributed in microglia and plays a pivotal role in neuroinflammation and neurodegeneration. Here studies are outlined that aimed at determining the mechanisms responsible for the anti-inflammatory and neuroprotective actions of luteolin using a rodent model of Parkinson's disease (PD) and specifically focusing on the role of TLR4 in this process. Methods: The mouse model of PD used in this experiment was established through a single injection of lipopolysaccharide (LPS). Mice were then subsequently randomly allocated to either the luteolin or vehicle-treated group, then motor performance and dopaminergic neuronal injury were evaluated. BV2 microglial cells were treated with luteolin or vehicle saline prior to LPS challenge. MRNA expression of microglial specific marker ionized calcium-binding adapter molecule 1 (IBA-1) and M1/M2 polarization markers, as well as the abundance of indicated pro-inflammatory cytokines in the mesencephalic tissue and BV2 were quantified by real time-polymerase chain reaction (RT-PCR) and Enzyme-linked Immunosorbent Assay (ELISA), respectively. Cell viability and apoptosis of neuron-like PC12 cell line co-cultured with BV2 were detected. TLR4 RNA transcript and protein abundance in mesencephalic tissue and BV2 cells were detected. Nuclear factor kappa-gene binding (NF-κB) p65 subunit phosphorylation both in vitro and in vivo was evaluated by immunoblotting. Results: Luteolin treatment induced functional improvements and alleviated dopaminergic neuronal loss in the PD model. Luteolin inhibited apoptosis and promoted cell survival in PC12 cells. Luteolin treatment shifted microglial M1/M2 polarization towards an anti-inflammatory M2 phenotype both in vitro and in vivo. Finally, it was found that luteolin treatment significantly downregulated both TLR4 mRNA and protein expression as well as restraining NF-κB p65 subunit phosphorylation. Conclusions: Luteolin restrained dopaminergic degeneration in vitro and in vivo by blocking TLR4-mediated neuroinflammation.
研究领域:
神经科学
·
药理学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Heng Lin,Hengyang Liu,Haosong Xi,Dangwei Li,Pengcheng Jiang,Yijun Wang,Siyi Cheng,Hong Jiang,Hongbing Deng,Xue Zhou,Lilei Yu
The occurrence of myocardial infarction (MI)-induced malignant ventricular arrhythmias (VAs) is closely associated with the hyperactivation of left stellate ganglion (LSG). Proinflammatory M1 macrophage is reported to aggravate sympathetic overactivation and cause VAs. Therefore, the depletion of M1 macrophage is anticipated to inhibit LSG overactivation and alleviate MI-induced VAs. Herein, oxygen-independent photodynamic therapy (Oi-PDT) combined with M1 macrophage targeting is applied to selectively deplete M1 macrophage in LSG and further treat MI-induced VAs. Oi-PDT, which overcomes the limitation of extremely dependence on oxygen content in traditional PDT, is constructed through the generation of oxidizing photogenerated holes (h + ) under the irradiation of near-infrared (NIR) light on the prepared Oi-PDT agent (PPSCD). Meanwhile, PPSCD targets M1 macrophage through conjunction with SR-A receptor. The selective consumption of M1 macrophage is attributed to both apoptosis and ferroptosis induced by h + , 1 O 2 , and O 2 •− generated in Oi-PDT. In vivo tests indicated neural activity experienced a notable reduction from 104.5 ± 2.9 to 51.5 ± 6.7 after MI with Oi-PDT treatment, thereby significantly inhibited VAs. The implementation of this study provides a promising strategy for selective consumption of M1 macrophages and treatment of VAs induced by MI.
研究领域:
心脏病学
·
免疫学
·
神经科学
·
治疗诊断学
✓ 已验证
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2021
·
IF 4.821
Chong Cai,Qi Zhang,Seyni Nidiaye,Honglin Yan,Wen Zhang,Xiaoqian Tang,Peiwu Li
Anti-idiotypic antibodies (AIds) display stable protein conformation, offering an alternative to conventional antigens in immunoassays. In this work, an anti-idiotypic variable domain of heavy-chain antibody (VHH) or nanobody named VHH C4 binding to monoclonal antibody (mAb) 2C9 against aflatoxin M 1 (AFM 1 ) was screened out from an alpaca immunized phage-displayed library. VHH C4 shows outstanding features in specificity and sensitivity, the IC 50 is 0.25 ng/mL and exhibit almost no cross-reactivity with other aflatoxin analogs. As our knowledge, it is the first report for developing an anti-idiotypic nanobody for AFM 1 . An environment-friendly competitive ELISA was developed using VHH C4 as a coating antigen. The results revealed a linear range from 0.10 ng/mL to 0.60 ng/mL, with a limit of detection (LOD) of 0.05 ng/mL. The recovery of spiked samples (pure milk, yogurt, and milk powder) ranged from 84.1% to 119.1%. The ELISA results of AFM 1 content in naturally contaminated samples were in good agreement with those determined by high performance liquid chromatography (HPLC). The results demonstrated that the nanobody VHH C4 is a promising alternative antigen in developing immunological methods for the detection of AFM 1 in dairy products.
研究领域:
免疫学
·
食品科学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
·
2024
·
IF 1.2
Yuzheng CAI,Ge GUO,Yankun FU,Xianqing HUANG,Tianlin WANG,Tiange LI
Simultaneous and rapid detection of various mycotoxins in food holds significant practical importance in the field of food processing and safety. In this study, a fluorescent aptasensor based on functionalized graphene oxide (FGO) is developed for simultaneous detection of aflatoxin B 1 (AFB 1 ) and aflatoxin M 1 (AFM 1 ). The two aptamers specific to AFB 1 and AFM 1 are labeled with Cy3 and Cy5 respectively. Both the aptamers can be adsorbed onto the surface of FGO through π - π stacking, resulting in fluorescence resonance energy transfer (FRET) between the fluorophore and FGO. The absence of target leads to quenching of fluorescence while presence of either aflatoxin causes interaction between corresponding aptamer and target, leading to release from FGO surface thereby turning on fluorescence signal. The limit of detection (LOD) for AFB 1 is determined as 8.7 pg/mL whereas for AFM 1 it is found to be 20.1 pg/mL, demonstrating fast and sensitive detection capability using this approach. Furthermore, the aptasensor exhibits good specificity and selectivity even under influence from other common interfering toxins. With its simplicity in operation and portability features, this sensor has potential applications for establishing sensitive and portable on-site detection methods for various mycotoxins.
研究领域:
食品安全
·
分析化学
·
生物传感技术
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）